Oat cell carcinoma of the lung is a rapidly fatal disease requiring initial aggressive combination chemotherapy. These sequential studies utilized combinations of active agents (cyclophosphamide, Adriamycin, and VP 16-213 as the basic regimen, and CCNU, methotrexate, vincristine, and procarbazine as an alternating regimen). Thirty-nine evaluable patients were entered onto the first study utilizing the basic combination with or without immunotherapy. Immunotherapy was not found useful for response or survival. The overall response rate for untreated patients was 97 percent with 63 percent complete remission. Previously irradiated patients did significantly worse than untreated patients. Median survival was 9-1/2 months and 16 months for patients with extensive and limited disease respectively. Among patients with limited disease, 4 of 13 survived more than 2 years, and 3 have survived disease-free greater than 28 months off all therapy. The successor study seeks to improve the complete remission rate and duration of response and survival by utilizing an alternating non-cross-resistant combination. Sixty-nine patients have been entered onto the second study, and preliminary evaluation shows no difference in the response rates or the duration of response. It is too early to develop stable response or survival data. Toxicity in these studies was manageable by dose modification.